Target intelligence / Profile preview

Cadherin-1 (CDH1) (CDH1)

Target
CDH1
Molecular classification
Cell adhesion molecule, Cadherin family, Receptor, Calcium-dependent glycoprotein
01

Overview

Cadherin-1, widely known as E-cadherin, is a pivotal calcium-dependent cell-cell adhesion molecule primarily expressed in epithelial tissues (UniProt P12830). It serves as a core component of adherens junctions, facilitating the structural cohesion of tissues by linking the extracellular environment to the intracellular actin cytoskeleton via catenin proteins (StatPearls, 2023). Beyond its structural role, E-cadherin is a critical regulator of signaling pathways involved in cell proliferation and differentiation. In the context of oncology, E-cadherin is often regarded as a tumor suppressor, as its functional loss is a hallmark of the epithelial-mesenchymal transition (EMT), which enables cancer cells to detach from the primary tumor and metastasize (PubMed: 25236395). Mutations in the CDH1 gene are strongly associated with hereditary diffuse gastric cancer and invasive lobular breast cancer (NCBI Gene: 999). Therapeutic interventions targeting E-cadherin, such as the small molecule ADH-1, aim to exploit its role in tumor stability and vascular integrity, though the ubiquity of E-cadherin in normal tissues necessitates careful management of potential toxicities (PubMed: 15254671).

Other names
E-cadherinEpithelial cadherinCD324UvomorulinCalcium-dependent adhesion protein, epithelialCAM 120/80
02

Mechanism of action

ADH-1 is a cyclic pentapeptide that acts as a competitive antagonist of E-cadherin-mediated adhesion by mimicking the His-Ala-Val (HAV) binding motif, thereby disrupting tumor-associated vasculature and inducing apoptosis in E-cadherin-expressing malignant cells (PubMed: 15254671).

03

Biological functions

Cell-cell adhesionSignal transductionTissue morphogenesisMaintenance of epithelial integrityEpithelial-mesenchymal transition (EMT) regulation
04

Disease associations

Cancer (Metastasis)Hereditary diffuse gastric cancer (HDGC)Invasive lobular breast cancerInfection (Listeria monocytogenes entry)Inflammation
05

Safety considerations

Disruption of normal epithelial barrier functionPotential induction of epithelial-mesenchymal transition (EMT) leading to increased metastasisToxicity to healthy epithelial tissues due to ubiquitous expression
06

Interacting drugs

ADH-1 (Exherin)
07

Biomarkers

CDH1 germline mutationsE-cadherin expression levels (Immunohistochemistry)Soluble E-cadherin (sE-cad) serum levels

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